Abstract
Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) has been characterized as a ubiquitin-like (Ubl) protein that affects a range of cellular processes across various pathways. In this study, mouse mammary epithelial cells (HC11 cell line) and UFL1 knockout (KO) mice were used to establish UFL1 knockdown models to explore the influence of UFL1 on milk protein and fat synthesis in the mouse mammary gland and the underlying mechanisms. This is the first study to show UFL1 localization in mouse mammary epithelial cells. UFL1 depletion by transfected UFL1 siRNA (siUFL1) caused aggravated apoptosis. In addition, UFL1 depletion suppressed milk protein synthesis-related protein level in vivo and in vitro. Conversely, ACACA and FASN expressions increased in UFL1-deficient mice. Moreover, UFL1 depletion increased triglyceride synthesis levels and inhibited the p-JNK expression. Importantly, the expression of proteins related to milk protein synthesis was decreased in JNK- and UFL1-deficient cells, whereas proteins related to milk fat synthesis showed the opposite trend, indicating that UFL1 affects milk protein and fat synthesis via the suppression of JNK activation. Overall, our findings indicate that UFL1 plays a key role in mammary milk and fat synthesis via JNK activation.
Highlights
The ubiquitin-fold modifier 1 (UFM1) conjugation system was characterized as a posttranslational modifier [1,2,3,4]
To investigate the Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) function in mammary epithelial cells, we explored UFL1 localization in mouse mammary epithelial cells (HC11 cell line)
SiUFL1-treated cells did not exhibit significant upregulation of triglyceride synthesis compared with the control group (P > 0:05, Figure 6(b)). These results suggest that UFL1 deficiency upregulates triglyceride synthesis and elevates ACACA and FASN protein levels in the mouse mammary gland
Summary
The ubiquitin-fold modifier 1 (UFM1) conjugation system was characterized as a posttranslational modifier [1,2,3,4]. Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an important E3-ligating enzyme of the UFM1 conjugation system, which is expressed in multiple tissues including heart, liver, intestinal, and pancreatic tissues [5,6,7,8,9]. It is well known that UFL1 is an indispensable component of this system given its involvement in various cellular processes, such as apoptosis [9, 10]. Targeted disruption of this protein is embryonically lethal, as it inhibits the embryonic development of the hematopoietic system 11.5 to 13.5 days after disruption in mice [9, 11]. Further elucidation of the posttranslational proteinmodifying system, such as UFL1, is critical to advance our understanding of various human organs and biological processes, regarding mammary gland development during pregnancy and lactation
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